Treatment stores

Roswell Park scientists identify potential new treatment target for pancreatic cancer

Scientists at Roswell Park Comprehensive Cancer Center have identified a potential new target for the treatment of pancreatic cancer. The study, published today in Cancer Cell, describes the team’s discovery of a fungus-activated pathway that fuels the production of a molecule found in pancreatic cancer cells, opening up a possible new treatment pathway. for patients with this devastating disease.

Pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all types of pancreatic cancer, is an aggressive and largely incurable disease, with limited treatment options and a 5-year survival rate of approximately 12% . PDAC tumors are dominated by cells that suppress the immune response to cancer and fuel disease progression, and currently available chemotherapy drugs often cannot penetrate the dense stroma surrounding PDAC tumors, making PDAC very aggressive. and resistant to therapy.

Pancreatic ductal adenocarcinoma is expected to become the second deadliest cancer by 2030 because it is so difficult to treat. Most current therapies are palliative and cannot ensure long-term survival, so there is an urgent need for new therapeutic targets. »

Prasenjit Dey, PhD, assistant professor of oncology, department of immunology at Roswell Park and senior study author

A hallmark of PDAC is the mutation of the Kras gene, which initiates tumor formation and leads to cancer progression. Using a preclinical model, Dr. Dey and his colleagues discovered that in PDAC cells, a particular oncogenic mutation -; KrasG12D-; triggers the production and release of the protein interleukin-33 (IL-33), which in turn stimulates tumor growth. In a proof-of-concept study, Roswell Park researchers confirmed that genetic knockout of IL-33 decreased tumor burden and prolonged survival. Surprisingly, they also discovered that the IL-33 pathway driving tumor growth depends on the fungi present in the tumor microenvironment.

“A healthy pancreas is generally sterile, with the notable exception of pancreatitis,” says Dr. Dey. “This is one of the first studies to show the presence of a fungus inside a tumor. Our work revealed an important link between the fungal mycobiome and the secretion of IL-33 in the tumours, which could change the way we treat PDAC.”

In the new study, the team identifies two types of fungi, Malassezia and Alternaria, which can invade the pancreas from the duodenum, promoting tumor progression. In a preclinical model, antifungal treatment significantly decreased PDAC tumor progression.

“This cooperative interaction between fungi and cancer cells in the tumor identifies a potential therapeutic strategy for PDAC,” says Dr. Dey. “Although the definitive link between fungal components and IL-33 secretion remains to be defined, our study suggests that antifungal treatment, combined with chemotherapy or immunotherapy to reduce or eliminate IL-33 in tumors, could be an effective treatment option for patients with this form of pancreatic cancer.”

Dr. Dey and colleagues are currently studying whether the combination of an antifungal agent and an immune checkpoint inhibitor can improve antitumor immune responses and outcomes in patients with PDAC.


Journal reference:

At the My., et al. (2022) Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer. Cancer cell.